1. Field of the Invention
The present invention relates to the preparation of enantiomerically enriched compounds using asymmetric catalysis. More particularly, the invention relates to the development of efficient catalysts and procedures for hydrogenation of tetra-substituted olefins of cyclic β-(acylamino)-acrylates to prepare enantiomerically enriched beta aminoacids.
2. Description of the Related Art
Enantiomerically pure β-amino acids and their derivatives are key structural elements of many natural products and drugs. They are also important chiral building blocks for the synthesis of β-peptides for biomedical research. For instance, trans-aminocyclopentanecarboxylic acid (1, trans-ACPC, FIG. 1) and trans-4-aminopyrrolidine-3-carboxylic acid (2, trans-APC) have been successfully used by Gellman et al. for constructing β-peptide antibiotics, while (1R,2S)-cis-aminocyclopentane-carboxylic acid (3, cispentacin) itself is a strong antifungal antibiotic.

Although some stoichiometric asymmetric synthesis or resolution methods of chiral cyclic β-amino acids and their derivatives have been reported [Berkessel, A.; Glaubitz, K.; Lex, J. Eur. J. Org. Chem. 2002, 2948. Yokota, Y.; Cortez, G. S.; Romo, D. Tetrahedron 2002, 58, 7075. Leplae, P. R.; Umezawa, N.; Lee, H.-S.; Gellman, S. H. J. Org. Chem. 2001, 66, 5629. Davies, S. G.; Ichihara, O.; Walters, I. A. S. Synlett 1993, 461. Yamazaki, T.; Zhu, Y.-F.; Probstl, A.; Chadha, R. K.; Goodman, M. J. Org. Chem. 1991, 56, 6644.], development of new, efficient, and catalytic asymmetric synthetic methods remains an important goal.
Although great success has been achieved in asymmetric hydrogenation of tri-substituted functionalized olefins, hydrogenation of tetra-substituted olefins is generally more difficult and much fewer successful results have been reported [Blaser, H.-U.; Spindler, Malan, C.; Pugin, B.; Spindler, F.; Steiner, H.; Studer, M. Adv. Synth. Catal. 2003, 345, 103].
Bruneau et al [Dupau, P.; Bruneau, C.; Dixneuf, P. H. Adv. Synth. Catal. 2001, 343, 331] and Rautenstrauch et al [Dobbs, D. A.; Vanhessche, K. P. M.; Brazi, E.; Rautenstrauch, V.; Lenoir, J.-Y.; Genet, J.-P.; Wiles, J.; Bergens, S. H. Angew. Chem. Int. Ed. 2000, 39, 1992] have reported hydrogenation of tetrasubstituted enamides and a vinylogous β-oxoester by employing Ru catalysts.
While many excellent chiral catalytic systems have been developed for hydrogenation of trisubstituted olefins of acyclic β-(acylamino)acrylates to make beta amino acids, enantioselective hydrogenation of tetra-substituted olefins of cyclic or acyclic β-(acylamino)acrylates remains an unexplored area. Accordingly, development of efficient catalysts and procedures for hydrogenation of tetra-substituted olefins of cyclic or acyclic β-(acylamino)acrylates for making beta aminoacids is a primary object of the present invention.